Cathelicidin-Related Antimicrobial Peptide Negatively Regulates Bacterial Endotoxin-Induced Glial Activation

• Published in: Cells (Basel, Switzerland) Vol. 11; no. 23; p. 3886
• Main Authors: Bhusal, Anup, Nam, Youngpyo, Seo, Donggun, Lee, Won-Ha, Suk, Kyoungho
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-12-2022; MDPI
• Subjects: Analysis; Animal models; Animals; Antimicrobial Cationic Peptides - metabolism; Antimicrobial Cationic Peptides - pharmacology; Antimicrobial peptides; astrocyte; Astrocytes; Bacteria; Bacterial infections; Brain; Care and treatment; Cathelicidins; Cell activation; Cell culture; Complications and side effects; CRAMP; Cytokines; Endotoxins; Experiments; Gene expression; Glial cells; Humans; Immune response; Infections; Inflammation; Innate immunity; Leucine; Lipopolysaccharides; Lipopolysaccharides - metabolism; Lipopolysaccharides - pharmacology; LPS; Mice; Mice, Inbred C57BL; Microglia; Microglia - metabolism; neuroinflammation; Neuronal-glial interactions; Nitric oxide; Peptides; Polymerase chain reaction; Tumor necrosis factor-TNF; South Korea; United States > US; Germany; CRAMP; neuroinflammation; astrocyte; microglia; LPS
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11233886

Recent studies have suggested that mouse cathelicidin-related antimicrobial peptide (CRAMP) and its human homologue leucine leucine-37 (LL-37) play critical roles in innate immune responses. Here, we studied the role of mouse CRAMP in bacterial endotoxin lipopolysaccharide (LPS)-induced neuroinflammation. CRAMP peptide treatment significantly inhibited LPS-mediated inflammatory activation of glial cells in culture. In the animal model of LPS-induced neuroinflammation, CRAMP expression was highly induced in multiple cell types, such as astrocytes, microglia, and neurons. Injection of exogenous CRAMP peptide significantly inhibited inflammatory cytokine expression and the reactivity of glial cells in the mouse brain following intraperitoneal or intracerebroventricular LPS administration. Altogether, results of the study suggest that CRAMP plays an important part in containment of LPS-induced neuroinflammatory responses, and that CRAMP can be exploited for the development of targeted therapies for neuroinflammatory conditions associated with bacterial infection.